It is the purpose of the proposed studies to determine whether there are anaerobic metabolic pathways, other than glycolysis, which are available to the renal cortex, papilla and inner medulla, during hypoxia and ischemia. From such information we may be able to obtain an understanding to permit the kidney to survive better during acute episodes of shock, or hemorrhage. We may also develop insight into a more effective way to preserve kidneys for transplantation. Our first objective is to determine whether anaerobic pathways (as manifested by the incomplete oxidation of certain substrates) make a significant contribution to renal energy production in the presence of low PO2. Once we have an understanding of renal metabolism in hypoxia in kidneys obtained from normal rats, the effects on renal metabolism of chronic diseases which impair delivery of O2 (anemia, altitude) or blood flow to the kidney such as in diabetes, aging, and hypertension can then be determined. In addition we may be able to determine how chronic anoxia (e.g. chronic pulmonary disease, acclimatization to altitude) affects the capacity of these nonglycolytic mitochondrial anaerobic metabolic pathways in the kidney. Therefore, using the isolated perfused rat kidney preparation, we plan first to determine the metabolic characteristics of the kidney as a function of: a) changes in O2 tension (PO2) of the perfusate; b) the availability of certain substrates, and c) the magnitude of the load of Na ion delivered into the proximal or distal nephron segments in kidneys from normal rats. Later studies are planned using kidneys from rats with streptozoticin diabetes or from rats of different ages. Longer range studies will include rats exposed to simulated high altitude (low PO2) or rats with chronic anemia.